Validation and quality control of replacement alternatives – current status and future challenges

Abstract Alternatives to animal testing have been developed mainly in the fields of toxicology and vaccine testing. Typical examples are the evaluation of phototoxicity, eye irritation or skin corrosion/irritation of cosmetics and industrial chemicals. However, examples can also be found in other biomedical areas, such the control of the quality of drug preparations for pyrogens or for the control of the production process of biologics, such as botulinum neurotoxin. For regulatory purposes, the quality, transferability and predictivity of an alternative method needs to be evaluated. This procedure is called the “validation process” of a new method. It follows defined rules, and several governmental institutions have been established to perform, supervise or advise on this process. As this often results in a delay of method implementation, different alternatives for the evaluation of a method's suitability and quality are under discussion. We describe here the principles of model development and quality control. We also give an overview on methods that have undergone validation. Strengths and shortcomings of traditional approaches are discussed, and new developments and challenges are outlined.